Fluorinated methyl aminoalkanoic acids of the Formula I ##STR2## wherein n represents 0, 1, 2 or 3 and
Y represents: PA1 Y represents CH.sub.2 F, CHF.sub.2 or CF.sub.3 and pharmacologically acceptable acid addition salts and certain derivatives of said acids of Formula VI are useful pharmacological agents, in particular as .gamma.-aminobutyric acid transaminase ("GABA-T") inhibitors (see U.K. Patent Specification No. 2005264 A). PA1 vinyl monofluoromethyl ketimine magnesium bromide; PA1 allyl difluoromethylketimine magnesium bromide; PA1 vinyl monofluoromethyl ketimine magnesium chloride; PA1 allyl difluoromethyl ketimine magnesium chloride; PA1 1-propenyl monofluoromethyl ketimine magnesium bromide; allyl monofluoromethyl ketimine magnesium bromide; PA1 2-butenyl monofluoromethyl ketimine magnesium bromide; PA1 2-butenyl difluoromethyl ketimine magnesium bromide; PA1 3-butenyl monofluoromethyl ketimine magnesium bromide; PA1 3-butenyl difluoromethyl ketimine magnesium bromide; PA1 4-pentenyl monofluoromethyl ketimine magnesium bromide; PA1 4-pentenyl difluoromethyl ketimine magnesium bromide; PA1 3-pentenyl difluoromethyl ketimine magnesium bromide; PA1 4-hexenyl monofluoromethyl ketimine magnesium bromide; PA1 3-butenyl-trifluoromethyl ketimine magnesium bromide; PA1 4-pentenyl-trifluoromethyl ketimine magnesium bromide; PA1 3-pentenyl-trifluoromethyl ketimine magnesium bromide. PA1 1-fluoro-2-amino-3-butene; PA1 1-fluoro-2-amino-3-pentene; PA1 1-fluoro-2-amino-4-pentene; PA1 1,1-difluoro-2-amino-4-pentene; PA1 1-fluoro-2-amino-5-hexene; PA1 1,1-difluoro-2-amino-6-heptene; PA1 1,1-difluoro-2-amino-5-hexane; PA1 1,1,1-trifluoro-2-amino-5-hexene; PA1 1-fluoro-2-amino-7-octene, and the like.
(a), when n represents 0, CH.sub.2 F, PA2 (b), when n represents 1, CH.sub.2 F or CHF.sub.2, and PA2 (c), when n represents 2 or 3, CH.sub.2 F, CHF.sub.2 or CF.sub.3 are, in general, useful as pharmacological or antibacterial agents.
Fluorinated methyl .gamma.-aminobutyric and .delta.-aminopentanoic acids of the Formula VI ##STR3## wherein n represents 2 or 3; and
.gamma.-Monofluoromethyl-.gamma.-aminobutyric acid of Formula VIII ##STR4## and pharmacologically acceptable salts are also reported to be glutamic acid decarboxylase inhibitors (see European Patent Specification No. 78100059.1).
.beta.-Monofluoro-.alpha.-aminopropionic acids (i.e. 3-fluoro alanines of the Formula IX) ##STR5## and pharmacologically acceptable salts are useful antibacterial agents (see U.K. Patent Specification No. 1367674). Compounds of Formula IX having the D-configuration are useful pharmacological anti-bacterial agents and 2-deutero-3-fluoro-D-alanine is particularly preferred for this purpose (see also U.K. Patent Specification No. 1367674).
It has recently been found that .beta.-fluorinated methyl .beta.-aminopropionic acids of the Formula VII ##STR6## wherein Y represents CH.sub.2 F or CHF.sub.2 and certain derivatives thereof are novel and useful pharmacological agents, in particular GABA-T inhibitors. The derivatives are the pharmaceutically acceptable esters and amides derived from the acid group, amides and urethanes derived from the amine group, lactams and salts. The preferred compounds are those of the Formula VIIa ##STR7## wherein
Y represents CH.sub.2 F or CHF.sub.2 ;
R.sub.2 represents C.sub.1 -C.sub.8 alkyl, -NR.sub.4 R.sub.5 (wherein each of R.sub.4 and R.sub.5 is hydrogen or C.sub.1 -C.sub.4 alkyl or an aminocarboxylic acid residue derived by removal of a hydrogen atom from the amino moiety of an L-aminocarboxylic acid; and
R.sub.3 is hydrogen, C.sub.2 -C.sub.5 alkylcarbonyl, C.sub.2 -C.sub.5 alkoxycarbonyl, phenyl-(C.sub.1 -C.sub.4 alkyl)carbonyl, phenyl (C.sub.1 -C.sub.4 alkoxy)carbonyl, phenylcarbonyl, phenoxycarbonyl or an aminocarboxylic acid residue derived by removal of an hydroxy group from the carboxy moiety of an L-aminocarboxylic acid; and the lactams thereof wherein R.sub.3 is hydrogen, and pharmacologically acceptable salts thereof.
It is an object of the present invention to provide a new and useful process for preparing fluorinated methyl aminoalkanoic acids of Formula I.
It is a particular, but not exclusive, object of the present invention to provide a new and useful process for preparing fluorinated alanines of the Formula IX.
It is an especial object of the present invention to provide a new and useful process for preparing 2-deutero-3-fluoro-D-alanine.